dbSNP rs11411759: TENM2:c.1310-6_1310-4delTTT (chr5-168062044-CTTT-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001395460.1(TENM2):c.1310-6_1310-4delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,333,826 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TENM2
NM_001395460.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.806

Publications

1 publications found

Variant links:

Genes affected

TENM2 (HGNC:29943): (teneurin transmembrane protein 2) Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; and retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TENM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395460.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	NM_001395460.1	MANE Select	c.1310-6_1310-4delTTT	splice_region intron	N/A	NP_001382389.1
TENM2	NM_001122679.2		c.1310-6_1310-4delTTT	splice_region intron	N/A	NP_001116151.1
TENM2	NM_001368145.1		c.854-6_854-4delTTT	splice_region intron	N/A	NP_001355074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	ENST00000518659.6	TSL:5 MANE Select	c.1310-15_1310-13delTTT	intron	N/A	ENSP00000429430.1
TENM2	ENST00000520394.5	TSL:1	c.614-15_614-13delTTT	intron	N/A	ENSP00000427874.1
TENM2	ENST00000519204.5	TSL:5	c.947-15_947-13delTTT	intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147066

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000145

AC:

AN:

172048

AF XY:

0.000182

show subpopulations

Gnomad AFR exome

AF:

0.000460

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000273

Gnomad EAS exome

AF:

0.000414

Gnomad FIN exome

AF:

0.000127

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000255

AC:

AN:

1333826

Hom.:

AF XY:

0.0000317

AC XY:

AN XY:

663068

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000100

AC:

AN:

29974

American (AMR)

AF:

0.0000790

AC:

AN:

37992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23996

East Asian (EAS)

AF:

0.0000277

AC:

AN:

36086

South Asian (SAS)

AF:

0.0000777

AC:

AN:

77218

European-Finnish (FIN)

AF:

0.000126

AC:

AN:

47760

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3916

European-Non Finnish (NFE)

AF:

0.0000127

AC:

AN:

1021628

Other (OTH)

AF:

0.0000362

AC:

AN:

55256

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.250

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

147066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71304

African (AFR)

AF:

0.00

AC:

AN:

40120

American (AMR)

AF:

0.00

AC:

AN:

14780

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5088

South Asian (SAS)

AF:

0.00

AC:

AN:

4696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66892

Other (OTH)

AF:

0.00

AC:

AN:

2012

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over